Clinical and transcriptomic characterization of patients with chronic lymphocytic leukemia harboring t(14;19): an ERIC study.

IF 13.4 1区 医学 Q1 HEMATOLOGY
Andrea Visentin,Enrico Gaffo,Moritz Fürstenau,Kerry A Rogers,Baliakas Panagiotis,Chenghua Cui,Cecelia Miller,Claudia Haferlach,Karla Plevova,David Oscier,Zadie Davis,Florence Nguyen-Khac,Eleonora Roncaglia,Gian Matteo Rigolin,Anastasia Athanasiadou,Fanny Baran-Marszak,Alberto Valiente,Maria José Terol,Pau Abrisqueta,Blanca Espinet,Anna Puiggros,Annalisa Martines,Laura Bonaldi,Francesca Romana Mauro,Lydia Scarfò,Thomas Chatzikonstantinou,Eugen Tausch,Karl-Anton Kreuzer,Arnon Kater,Francesc Bosch,Michael Doubek,Panagiotis Panagiotidis,Olga Kalashnikova,Federica Frezzato,Giulia Calabretto,Valeria Ruocco,Silvia Orsi,Alessandro Cellini,Francesco Angotzi,Andrea Serafin,Shuhua Yi,Barbara Eichhorst,Jennifer A Woyach,Antonio Cuneo,Paolo Ghia,Kostas Stamatopoulos,Livio Trentin,Stefania Bortoluzzi
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引用次数: 0

Abstract

In chronic lymphocytic leukemia (CLL), the role of complex karyotype (CK) for prognostic stratification remains a topic of debate, and the impact of specific cytogenetic abnormalities is still unclear. This study aims to investigate the clinical and biological features of CLL with t(14;19)(q32;q13) (tCLL) involving the BCL3 gene. Patients with tCLL were younger and more commonly presented unmutated IGHV gene, subset #8 stereotypy, trisomy of chromosome 12, and complex karyotype than other patients without t(14;19) (oCLL). The presence of t(14;19) was associated with a shorter time to treatment and overall survival compared to oCLL. Gene expression analysis revealed a unique transcriptome profile in tCLL, characterized by the upregulation of BCL3 and the activation of B-cell receptor, PI3K-Akt. Conversely, apoptosis-related pathways were suppressed in tCLL. While the BTK gene was upregulated, the BCL2L11 gene, coding for the pro-apoptotic protein BIM, was downregulated. Notably, patients with tCLL were characterized by a trend (p = 0.058) for a longer time to the next treatment with BTK inhibitors (BTKi) compared to those treated with a venetoclax-based (Ven-based) regimen. We underscore the adverse outcomes of tCLL, its distinct molecular features and gene expression patterns. Therefore, our data suggest that identifying tCLL could help tailor therapeutic approaches.
慢性淋巴细胞白血病患者携带t的临床和转录组学特征(14;19):一项ERIC研究。
在慢性淋巴细胞白血病(CLL)中,复杂核型(CK)在预后分层中的作用仍然是一个有争议的话题,特异性细胞遗传学异常的影响仍然不清楚。本研究旨在探讨涉及BCL3基因的t(14;19)(q32;q13) (tCLL) CLL的临床和生物学特征。tCLL患者比其他无t的患者更年轻,更常见的表现为未突变的IGHV基因、8亚群定型、12号染色体三体和复杂的核型(14;19)(oCLL)。与oCLL相比,t(14;19)的存在与更短的治疗时间和总生存期相关。基因表达分析揭示了tCLL中独特的转录组谱,其特征是BCL3上调和b细胞受体PI3K-Akt的激活。相反,凋亡相关通路在tCLL中被抑制。BTK基因上调,编码促凋亡蛋白BIM的BCL2L11基因下调。值得注意的是,与以venetoclax为基础(vin为基础)的治疗方案相比,tCLL患者的特征是BTK抑制剂(BTKi)治疗的时间更长(p = 0.058)。我们强调tCLL的不良后果,其独特的分子特征和基因表达模式。因此,我们的数据表明,识别tCLL可以帮助定制治疗方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Leukemia
Leukemia 医学-血液学
CiteScore
18.10
自引率
3.50%
发文量
270
审稿时长
3-6 weeks
期刊介绍: Title: Leukemia Journal Overview: Publishes high-quality, peer-reviewed research Covers all aspects of research and treatment of leukemia and allied diseases Includes studies of normal hemopoiesis due to comparative relevance Topics of Interest: Oncogenes Growth factors Stem cells Leukemia genomics Cell cycle Signal transduction Molecular targets for therapy And more Content Types: Original research articles Reviews Letters Correspondence Comments elaborating on significant advances and covering topical issues
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